Yan F, Fujimori DG

RlmN and Cfr are Radical SAM enzymes that modify a single adenosine
nucleotide--A2503--in 23S ribosomal RNA. This nucleotide is positioned within the
peptidyl transferase center of the ribosome, which is a target of numerous
antibiotics. An unusual feature of these enzymes is their ability to carry out
methylation of amidine carbons of the adenosine substrate. To gain insight into
the mechanism of methylation catalyzed by RlmN and Cfr, deuterium labeling
experiments were carried out. These experiments demonstrate that the newly
introduced methyl group is assembled from an S-adenosyl-L-methionine
(SAM)-derived methylene fragment and a hydrogen atom that had migrated from the
substrate amidine carbon. Rather than activating the adenosine nucleotide of the
substrate by hydrogen atom abstraction from an amidine carbon, the
5'-deoxyadenosyl radical abstracts hydrogen from the second equivalent of SAM to
form the SAM-derived radical cation. This species, or its corresponding sulfur
ylide, subsequently adds into the substrate, initiating hydride shift and
S-adenosylhomocysteine elimination to complete the formation of the methyl group.
These findings indicate that rather than acting as methyltransferases, RlmN and
Cfr are methyl synthases. Together with the previously described 5'-deoxyadenosyl
and 3-amino-3-carboxypropyl radicals, these findings demonstrate that all three
carbon atoms attached to the sulfonium center in SAM can serve as precursors to
carbon-derived radicals in enzymatic reactions.

This publication refers to following proteins:

Cfr (Staphylococcus sciuri)

RlmN (Escherichia coli)

Entry added on: 2011-10-04 14:14:55.377685, by a user: magda

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